Global Insight Perspective | |
Significance | The CHMP has recommended that Sanofi-Aventis's obesity drug Acomplia (rimonabant) be suspended from marketing in the European Union. |
Implications | The move will affect sales in 18 EU member states, and will reduce the already muted turnover for Acomplia. Sanofi-Aventis has described the suspension as temporary, but has also confirmed that it will work with other countries to implement equivalent decisions on marketing suspension. |
Outlook | From a sales point of view, the fallout will not be huge for Sanofi-Aventis, but the decision does bring to an end the group's hopes of developing the drug as a blockbuster. With a change in leadership ahead, reliance on the rimonabant molecule is likely to diminish. |
French pharmaceutical company Sanofi-Aventis has again suffered a crushing blow to its ambitions for obesity drug Acomplia (rimonabant), following a recommendation by the EMEA's Committee for Medicinal Products for Human Use (CHMP) to suspend the drug's marketing authorisation across the European Union. The recommendation has been passed on to the European Commission, which will need to make the final decision on the suspension. If it does, which is extremely likely, it will affect the 18 EU member states in which Acomplia is presently marketed.
Acomplia's EU Market Reach | |
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The CHMP's decision was reached after it conducted an internal review of all available information on Acomplia's risks and benefits, including post-marketing studies. The review was triggered under Article 20 of Regulation (EC) No 726/2004, which is designed to tackle public health concerns over a centrally authorised drug. The CHMP concluded that post-marketing data indicates approximately twice the risk of psychiatric disorders for patients prescribed Acomplia than for those taking placebos. In addition, Acomplia's efficacy was called into question after the CHMP said that its effectiveness was "more limited than expected on the basis of clinical trials", as available post-marketing data suggest that patients only take the drug for a short period of time.
Sanofi-Aventis—which has been careful to describe the recommendation as one for a temporary suspension—has pledged to co-operate fully with the EMEA and the European Commission regarding Acomplia. The company says it remains committed to developing the drug to its full potential, and has confirmed that it will continue its clinical trial programme on the active ingredient rimonabant at all levels except Phase IV (post-marketing trials). Sanofi-Aventis has also said that it will approach public health regulators in countries outside Europe to determine how best to promptly implement a decision similar or equivalent to that reached by the EMEA.
Acomplia first gained EU approval in June 2006, and is marketed in select EU countries as an adjunct to diet and exercise for the treatment of obese patients or overweight patients with associated risk factors. A warning on the risk of psychiatric effects including depression has been included in the drug's European product information since it was first approved, although in the intervening years this has been supplemented by several other safety measures (see table below). A U.S. FDA advisory committee warned against approving the drug in the United States the following year due to concerns over psychiatric side-effects, and Sanofi-Aventis eventually chose to withdraw its marketing application (see France: 2 July 2007: Zimulti Marketing-Application Withdrawal Slims Down U.S. Prospects for Sanofi-Aventis). Global turnover of Acomplia amounted to 79 million euro (US$99.1 million) in 2007.
Acomplia's EU Safety Timeline | |
June 2006 | EU approval. Warning included in product information that Acomplia should not be initiated in patients with hepatic or renal impairment or patients with uncontrolled serious psychiatric illnesses such as major depression. |
July 2007 | CHMP recommends contraindicating Acomplia in patients with ongoing major depression or who have been prescribed anti-depressants. |
May 2008 | CHMP recommends updating product information to reflect that depression may occur as a side-effect of Acomplia in patients with no obvious risk factors beyond obesity. |
October 2008 | CHMP recommends suspending EU marketing authorisation for Acomplia. |
Outlook and Implications
With the CHMP now saying that Acomplia's risks are unable to be addressed through further risk-management and minimisation processes, Sanofi-Aventis's interpretation of the marketing suspension as "temporary" may be wishful thinking. In its obesity indication at least, the drug is highly unlikely to regain the confidence of European health regulators, which will have repercussions on the remaining markets where Acomplia is sold. Sanofi-Aventis's best bet for the drug is its development in other indications such as Type 2 diabetes, for which late-stage clinical trials are already underway and a regulatory filing is tentatively scheduled for 2009 (see France: 4 April 2008: Sanofi-Aventis "On Target" to File Six New Drugs for Approval). Even here, however, the level of scrutiny over the drug's links to adverse psychiatric events would render an immediate approval doubtful. Additionally, the imminent replacement of CEO Gérard Le Fur by Chris Viehbacher could also herald a move away from over-reliance on the rimonabant molecule as growth strategy. Rimonabant's development was overseen by Le Fur for a decade, and his departure—widely believed to be tied to the drug's failure to set the markets alight (see France: 10 September 2008: Shareholders Behind Proposed Change of Direction at Sanofi-Aventis)—is likely to shake up Sanofi-Aventis's future approach to R&D.